Redox and proteolytic regulation of cardiomyocyte β1-adrenergic receptors - a novel paradigm for the regulation of catecholamine responsiveness in the heart

Abstract

Conventional models view β₁-adrenergic receptors (β₁ARs) as full-length proteins that activate signaling pathways that influence contractile function and ventricular remodeling - and are susceptible to agonist-dependent desensitization. This perspective summarizes recent studies from my laboratory showing that post-translational processing of the β₁-adrenergic receptor N-terminus results in the accumulation of both full-length and N-terminally truncated forms of the β₁AR that differ in their signaling properties. We also implicate oxidative stress and β₁AR cleavage by elastase as two novel mechanisms that would (in the setting of cardiac injury or inflammation) lead to altered or decreased β₁AR responsiveness.

Keywords: cardiomyocytes; elastase; oxidative stress; proteolysis; β1-adrenergic receptors.